The neuroprotective effect of chlormethiazole on ischaemic neuronal damage following permanent middle cerebral artery ischaemia in the rat.

The ability of chlormethiazole to protect against ischaemic cell damage in a rat model of permanent focal ischaemia has been examined. Chlormethiazole (1 mmol/kg) was administered intraperitoneally either 1 or 3 h after occlusion of the middle cerebral artery with an intraluminal filament. Twenty four hours after the start of occlusion there was histological evidence for ischaemic damage in both cortex and striatum. The volume of ischaemic damage in control (saline injected) animals was 310 +/- 25 mm3 (mean +/- SEM; n = 6). Chlormethiazole administered 1 h after occlusion reduced this damage by 58% (128 +/- 40 mm3; n = 6; P < 0.01), protection being observed in both brain regions. The drug was ineffective when given 3 h after occlusion (304 +/- 25 mm3; n = 5). Chlormethiazole had no effect on body temperature, mean arterial blood pressure, blood pH, pO2 or pCO2, but did induce mild bradycardia. Chlormethiazole therefore appears to be an effective neuroprotective agent in this model of permanent ischaemia, complementing previous data on the efficacy of this drug in other focal and global models of cerebral ischaemia.